In this research project we are analyzing the functions of the evolutionary conserved zinc transcription factors Bcl11a and Bcl11b as well as their downstream genetic pathways that are relevant to the development of neocortical projection neurons. These neurons are the principal cells of our brains and can be divided into different subtypes based on their molecular profile, projection behavior, as well as neurophysiological properties. Both BCL11A and BCL11B have been implicated in neurodevelopmental diseases associated with intellectual disability, autism spectrum and speech disorders. We are using genetic models, FACS, ATAC-Seq, and scRNA-Seq to uncover conserved co-regulated molecular downstream programs in projection neuron subtypes, that are further explored by molecular biology, biochemistry, histology, imaging, and experimental embryology approaches. We expect to uncover novel molecular mechanisms that are important for neocortical development and also relevant to human disease.

Project Team
Dr. Christoph Wiegreffe (Project Lead)
Yun Chen
Jacqueline Andratschke
Luisa Schmid

Related Publications
Wiegreffe et al., 2015 Neuron
Wiegreffe et al., 2017 Journal of Vis. Exp.
Wiegreffe et al., 2022 EMBO Reports

Collaborators
Christian Mayer, MPI, Munich